Ipilimumab and nivolumab plus radioembolization as salvage therapy for atezolizumab and bevacizumab refractory hepatocellular carcinoma resulting in complete pathologic response.

Unresectable hepatocellular carcinoma unresponsive to first-line immunotherapy has a poor prognosis with modest response to tyrosine kinase inhibitors in the second line. In these patients, the benefit of local therapy with immunotherapy rechallenge is unknown. Radioembolization is a guideline-supported locoregional therapy for HCC that has shown the potential for synergy in combination with immunotherapy. This report describes a patient with veno-invasive HCC and extrahepatic invasion of the right kidney which progressed on atezolizumab and bevacizumab and was subsequently downstaged to resection with ipilimumab and nivolumab plus radioembolization yielding a complete pathologic response. The patient is currently more than 2 years since diagnosis without evidence of disease recurrence.

Intra-arterial locoregional therapies for Intrahepatic Cholangiocarcinoma.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is the 2nd most common primary liver malignancy. For nonsurgical candidates, the primary treatment option is systemic chemotherapy, which can be combined with locoregional therapies to enhance local control. Common intra-arterial locoregional therapies include transarterial hepatic embolization, conventional transarterial chemoembolization, drug-eluting bead transarterial chemoembolization, transarterial radioembolization with Yttrium-90 microspheres, and hepatic artery infusion. This article aims to review the latest literature on intra-arterial locoregional therapies for treating ICC. AREAS COVERED: A literature search was conducted on PubMed using keywords: intrahepatic cholangiocarcinoma, intra-arterial locoregional therapy, embolization, chemoembolization, radioembolization, hepatic artery infusion, and immunotherapy. Articles from 2008 to 2024 were reviewed. Survival data from retrospective and prospective studies, meta-analyses, and clinical trials were evaluated. EXPERT OPINION: Although no level I evidence supports the superiority of any specific intra-arterial therapy, there has been a shift toward favoring radioembolization. In our expert opinion, radioembolization may offer superior outcomes when performed by skilled operators with meticulous planning and personalized dosimetry, particularly for radiation segmentectomy or treating lobar/bilobar disease in appropriate candidates.

Ruptured Hepatocellular Carcinoma: A Case Report.

Hepatocellular carcinoma (HCC) is one of the most common primary liver tumors in the world. In the United States, it is very uncommon for the liver mass to spontaneously rupture, especially if it has already been treated with embolization. Prompt diagnosis and treatment are necessary to improve the overall prognosis. Unfortunately, even with treatment, the patient can still rapidly decline. We present a case of a patient who was diagnosed with HCC and received treatment with transarterial radioembolization (TARE) with yttrium-90 (Y90). Despite this, the patient's liver mass grew and spontaneously ruptured. Although the patient received additional embolizations for his mass, he still deteriorated and eventually expired.

Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma.

Immunotherapy and the implementation of more aggressive treatment schemes for locally advanced hepatocellular carcinomas have expanded the boundaries of curative options. Because of these advancements, patients who were once considered beyond the aim of a cure are now eligible for liver transplantation and resection.

Liver transplantation for organ failure following multiple locoregional treatments for breast cancer metastasis.

Patients with nonresectable breast cancer liver metastasis (BCLM) face a dismal prognosis. Despite liver transplantation (LT) for metastatic liver tumors having recently shown good results, BCLM represents an absolute contraindication. This study aimed to investigate the potential for long-term survival after LT for BCLMs in a patient experiencing end-stage liver disease, following multiple oncologic treatments. In July 2019, we performed a deceased donor LT on a 41-year-old female with BCLM controlled with human epidermal growth factor receptor 2 targeted therapy, who developed liver failure following multiple locoregional liver-directed treatments. The primary tumor was treated with surgical resection and adjuvant chemoradiation in 2000. The procedure was performed under a protocol approved by the local ethical committee, and by the Italian National Transplant Center. A 12-month treatment with trastuzumab was performed immediately after LT. Immunosuppression following transplantation was undertaken without steroids, and with everolimus. The patient completed 12 months of follow-up without recurrence. Trastuzumab was then withdrawn. Fifteen months after LT, a liver recurrence occurred that was treated with chemotherapy. In October 2021, she developed 2 brain lesions that were treated with stereotactic radiation. The patient is still alive, with a positron emission tomography/computed tomography performed in January 2024 showing no disease. LT for this patient with BCLM of extreme selectivity showed a good clinical outcome. Perioperative systemic treatment and tumor control are necessary. A specific protocol should be discussed within a multidisciplinary team, and with local and national authorities. Even if tumor recurrence occurs, multimodal therapy can control the disease.

Cone Beam Computed Tomography for the Interventional Oncologist: A Practical Approach.

Transarterial treatment of liver tumors is becoming increasingly common and is considered first- or second-line therapy for many tumor types and stages. Such therapies are heavily dependent on imaging during the procedures; while angiography remains the mainstay of intraprocedural therapies, cone beam computed tomography (CBCT) is becoming increasingly commonly used to guide therapy. This article describes the role of CBCT during transarterial therapies and offers guidance as to how CBCT can be optimally used for these procedures.

Imaging for Interventional Radiology Liver-Directed Therapies for Neuroendocrine Liver Metastases.

Neuroendocrine tumors are an indolent, heterogeneous group of tumors that primarily arise from the gastropancreatic tract and lungs. Most patients present with liver metastases at the time of diagnosis, which cause significant morbidity and mortality due to excess hormone secretion, bile duct obstruction, and liver damage. A small percentage of these patients are eligible for potential cure through surgical resection. However, interventional radiology provides liver-directed therapies, such as percutaneous ablation, transarterial embolization, chemoembolization, and radioembolization, for palliative care and potential bridging to debulking and surgical resection of neuroendocrine liver metastases. This article aims to provide a brief overview of these liver-directed therapies focusing on the pre-, intra-, and postprocedural imaging findings.

Angiographic Aspects of Transarterial Radioembolization: A Comparison of Technical Options to Avoid Extrahepatic Microsphere Depositions.

The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions.

Voxel-based dosimetry with integrated Y-90 PET/MRI and prediction of response of primary and metastatic liver tumors to radioembolization with Y-90 glass microspheres.

PURPOSE: In this study, we aimed to evaluate the response of the primary and metastatic liver tumors to radioembolization with 90Y glass microspheres and investigate its correlations with dosimetric variables calculated with 90Y PET/MRI. METHODS: In this ambispective study, 44 patients treated with 90Y glass microspheres and imaged with 90Y PET/MRI were included for analysis. Dosimetric analysis was performed for every perfused lesion using dose-volume histograms. Response was assessed by comparing pre-treatment and follow-up total lesion glycolysis (TLG) values derived from 18F-FDG PET imaging. The relationship between ΔTLG and log-transformed dosimetric variables was analyzed with linear mixed effects regression models. ROC analyses were performed to compare discriminatory power of the variables in predicting response and complete response. RESULTS: Regression and ROC analyses demonstrated that mean tumor dose and almost all D values were statistically significant predictors of treatment response and complete treatment response. Specifically, D60, D70 and D80 values exhibited significantly higher discriminatory power for predicting treatment response compared to the mean dose (Dmean) delivered to tumor. High specificity cut-off values to predict response were determined as 160.75 Gy for Dmean, 95.50 Gy for D60, 89 Gy for D70, and 59.50 Gy for D80. Similarly, high-specificity cut-off values to predict complete response were 262.75 Gy for Dmean, 173 Gy for D70, 140.5 Gy for D80, and 100 Gy for D90. CONCLUSION: In this study, we demonstrated that voxel-based dosimetry with post-treatment 90Y PET/MRI can predict response to treatment. D60, D70 and D80 variables also did have greater discriminatory power compared to Dmean in prediction of response. In addition, we present high-specificity cut-offs to predict response (CR + PR) and complete response (CR) for both Dmean and several D variables derived from dose-volume histograms.

Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy.

Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.

Mortality and postinterventional complications after ablative treatment of liver malignancies: A cohort study of 4374 patients.

PURPOSE: Ablative therapies for primary and secondary liver malignancies are increasingly adopted in current guidelines. Nevertheless, surgical resection remains the gold standard in most curative therapy settings. Extensive studies on mortality and morbidity after ablative treatment of the liver are missing. We investigated complications and mortality after ablative treatment in a large, unselected study cohort. MATERIALS AND METHODS: Standardized patient and treatment data in 4374 percutaneous and angiographic ablative procedures of the liver from the DRG-based hospital reimbursement system (diagnosis-related groups) of an academic hospital in Germany were retrospectively evaluated. We analyzed descriptive patient data, length of stay (LOS), pre-existing medical conditions, previous gastrointestinal surgeries, severe complications, and occurrence of death. RESULTS: Treatment of secondary liver malignancies constituted over two-thirds of all procedures (71%, n = 3053). The mean LOS was 4.1 ± 3.5 days. Severe complications were documented in 1.4% and in-house death in 0.2% of cases, significantly more often after treatment with chemoembolization of primary liver malignancies (p = 0.003; p = 0.0001). Previous partial liver resection, partial bowel resection, and chronic renal failure were independent risk factors for the occurrence of severe complications. CONCLUSION: Severe complications and in-hospital death are rare in the treatment of primary and secondary liver malignancies with percutaneous and angiographic procedures. They are a viable alternative or addition to a surgical approach in treating liver lesions.

Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: An Updated Meta-analysis and Meta-regression.

PURPOSE: Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA. METHODS: We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity. RESULTS: We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naïve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naïve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naïve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe. CONCLUSIONS: Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naïve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.

Maximizing therapeutic outcomes in hepatocellular carcinoma: Insights into combinatorial strategies.

In this editorial, we review the article by Ma and colleagues, published in the World Journal of Gastrointestinal Oncology. Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Although transarterial chemoembolization (TACE) has been used effectively for several years, particularly in patients with intermediate-stage HCC, the quest for the optimal combination therapy to enhance its efficacy and HCC treatment strategies persists. Combining TACE with tyrosine kinase inhibitors (TKIs) like sorafenib or lenvatinib has shown confusing results in improving both progression-free survival and overall survival. Similarly, combining TACE with immune checkpoint inhibitors (ICIs) has demonstrated potential efficacy by reshaping the tumor microenvironment and activating immune responses. Recent studies suggest combining TACE with TKIs and ICIs may offer synergistic effects. Additionally, combining TKIs and ICIs with other local treatments like microwave ablation or hepatic arterial infusion chemotherapy has shown promise in enhancing efficacy. However, more extensive prospective studies are needed to validate these findings. Overall, these combinations represent a promising direction in HCC management, emphasizing the need for further research to optimize treatment outcomes.

Evaluation of a prototype metal artifact reduction algorithm for cone beam CT in patients undergoing radioembolization.

Metal artifacts notoriously pose significant challenge in computed tomography (CT), leading to inaccuracies in image formation and interpretation. Artifact reduction tools have been designed to improve cone beam computed tomography (CBCT) image quality by reducing artifacts caused by certain high-density materials. Metal artifact reduction (MAR) tools are specific algorithms that are applied during image reconstruction to minimize or eliminate artifacts degrading CBCT images. The purpose of the study is to evaluate the effect of a MAR algorithm on image quality in CBCT performed for evaluating patients before transarterial radioembolization (TARE). We retrospectively included 40 consecutive patients (aged 65 ± 13 years; 23 males) who underwent 45 CBCT examinations (Allura FD 20, XperCT Roll protocol, Philips Healthcare, Best, The Netherlands) in the setting of evaluation for TARE between January 2017 and December 2018. Artifacts caused by coils, catheters, and surgical clips were scored subjectively by four readers on a 5-point scale (1 = artifacts affecting diagnostic information to 5 = no artifacts) using a side-by-side display of uncorrected and MAR-corrected images. In addition, readers scored tumor visibility and vessel discrimination. MAR-corrected images were assigned higher scores, indicating better image quality. The differences between the measurements with and without MAR were most impressive for coils with a mean improvement of 1.6 points (95%CI [1.5 1.8]) on the 5-point likert scale, followed by catheters 1.4 points (95%CI [1.3 1.5]) and clips 0.7 points (95%CI [0.3 1.1]). Improvements for other artifact sources were consistent but relatively small (below 0.25 points on average). Interrater agreement was good to perfect (Kendall's W coefficient = 0.68-0.95) and was higher for MAR-corrected images, indicating that MAR improves diagnostic accuracy. A metal artifact reduction algorithm can improve diagnostic and interventional accuracy of cone beam CT in patients undergoing radioembolization by reducing artifacts caused by diagnostic catheters and coils, lowering interference of metal artifacts with adjacent major structures, and improving tumor visibility.

Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose-response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.

Immune modulation in untreated, contralateral hepatic metastases after Y90-radioembolization of microsatellite stable (MSS) colorectal cancer.

PURPOSE: To assess immunogenic effects in unembolized contralateral tumor after single lobar Y90-radioembolization (SIRT) of colorectal liver metastases(CRLM). MATERIAL AND METHODS: The analysis comprised 10 patients with microsatellite stable (MSS) CRLM scheduled for staged treatment in the prospective BLINDED trial. Eligibility criteria included bilobar metastatic disease with >5 lesions without any treatment within 3 weeks. Baseline biopsy was followed by initial SIRT treatment of one liver lobe, followed by a second biopsy of yet untreated tumors in the other liver lobe at a median of 13 (4-49) days immediately prior to second treatment. Tumor biopsies and peripheral blood mononuclear cells (PBMC) were collected before treatments for immune cell analysis. Patients were stratified into "responders" and "non-responders" based on tumor control or progression during follow up. RESULTS: At baseline, responders (n=4) displayed lower concentrations of FoxP3+ cells and co-location of CD4+FoxP3+ cells than non-responders (both p=0.02) in tumor tissues. At second biopsy, non-responders showed a higher CD68+ macrophage density (p=0.0014) than responders. Responders displayed fewer CD4+FoxP3+ T cells than CD8+ T cells at all timepoints (p=0.02 and p=0.0428). Non-responders demonstrated a trending increase of CD68+ macrophages (p=0.062), as well as a higher CD8+PD1+/CD8+ ratio (p=0.062). PBMC of non-responders displayed lower CD8+PD1+ T cells and CD8+PD1+/CD8+ ratio at both timepoints. CONCLUSION: SIRT induces local immunogenic effects in non-exposed MCC CRLM, as well as systemic exhaustion of immune cells in non-responders. Clinical implications such as a prognostic role or synergism of SIRT and checkpoint inhibition in MSS CRLM warrant further investigation.

Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study.

BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N = 143) demonstrated superior outcomes vs Chemo (N = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).

Paraneoplastic Diarrhea From Medullary Thyroid Carcinoma Resolved With Yttrium-90 Radioembolization of Liver Metastases.

Medullary thyroid carcinoma (MTC) can often have an indolent course despite distant metastatic disease. Additionally, given that metastatic MTC is incurable and systemic therapies have non-negligeable toxicities, localized treatments are often favored in presence of oligo-progressive disease. Transarterial radioembolization (TARE) with yttrium-90 (Y90) has emerged as a safe and efficacious treatment for nonresectable primary and metastatic liver tumors, yet data supporting its use in metastatic MTC are limited. We present the case of a patient with hereditary MTC and large bilobar liver metastases who demonstrated tumor response and resolution of their paraneoplastic diarrhea following TARE with Y90 microspheres.

Thymic Carcinoma Presenting as a Mediastinal Mass Resembling a Cardiac Tumor.

Thymoma and thymic carcinomas are a few of the rarest malignancies seen in humankind. They are mostly seen in the Asian population, many of which are reported in the Southeast Asia region like Japan, China, Vietnam, etc. They usually can be a sequela of other underlying conditions such as myasthenia gravis or some unknown mutations that express later in life.   Our patient is a young 41-year-male, a healthy and active individual who presented for evaluation of acute shortness of breath, two months after recovering from SARS-CoV-19 infection. His shortness of breath progressed while on oxygen and diuretics, a Point of Care Ultrasound (POCUS) showed cardiac tamponade and moderate pleural effusion. A Computerized Tomographic (CT) scan of the chest/abdomen/pelvis showed cardiomegaly, pleural effusion, and a mass abutting the heart. A pericardiocentesis revealed malignant cells. Thymic carcinoma was confirmed with a core biopsy and the patient was initiated on treatment rapidly to help improve symptoms and contain the growing mass.  .